A grafted copolymer-based nanomicelles for topical ocular delivery of everolimus: Formulation, characterization, ex-vivo permeation, in-vitro ocular toxicity, and stability study.

Treatment of posterior uveitis via topical route is desirable but cannot be achieved by conventional drug delivery strategies. Therefore, the aim of this study is to develop a topical nanomicellar formulation of an immunosuppressant drug, everolimus using Soluplus®, a grafted copolymer of polyvinyl caprolactam-polyvinylalcohol-polyethyleneglycol (PVCL-PVA-PEG) for improved permeation through ocular epithelia with minimal or no irritation resulting in enhanced ocular bioavailability at the posterior segments of the eye for the treatment of uveitis. Soluplus-everolimus nano micelles were found to have a low CMC (7.2 µg/ml) and 65.55 nm in size. The prepared nanomicelles were characterized for surface morphology by TEM, SEM, and AFM and found to have spherical particles with a smooth surface. The nanomicelles were found to have high encapsulation efficiency and result in sustained release of everolimus when compared with everolimus suspension. The everolimus nanomicelles showed significantly higher permeation across goat cornea than everolimus suspension (p<0.001). CLSM of prepared nanomicelles confirmed the deeper permeation through the goat cornea. These results indicated the significantly higher accessibility and improved drug bioavailability thus, everolimus nanomicelles could be considered a promising topical drug delivery nanocarrier for treating uveitis.